The overall objective of the proposed research is to contribute to the noninvasive detection and evaluation of myocardial pathology based on quantitative ultrasonic characterization of the tissue itself, as opposed to assessment of dimensions or motion. Previous research suggests that integrated (frequency averaged) backscatter shows promise for myocardial tissue characterization. The time averaged (over the heart cycle) integrated backscatter is elevated in ischemic myocardium. Furthermore, myocardial contraction and relaxation are paralleled by a cyclic variation in integrated backscatter, which is reduced substantially with even brief ischemia in dogs, and which recovers with reperfusion. A significant obstacle for extending these findings to studies of patients results from the fact that spatial orientation of the structure of myocardium gives rise to systematic variations (i.e., anisotropy) in its ultrasonic properties. Clinical applications of ultrasonic tissue characterization require measurements to be made with the propagation of ultrasound at varying angles with respect to the average fiber orientation of the heart and throughout the contraction-relaxation cycle. Successful characterization of myocardium with ultrasound will require compensation for the effects of this angular variation. We propose to investigate the anisotropy in the ultrasonic properties of the heart and their relationships to cardiac-dependent variation in myocardial backscatter: 1) by measuring the angular dependence of myocardial backscatter in vivo in open- and closed-chest dogs, 2) by characterizing the mechanisms responsible for the observed anisotropy in myocardium through application of a time domain low contrast approximation for the scattering of ultrasonic waves from cylindrical scatterers, and 3) by evaluating the consequences of anisotropy for clinical tissue characterization carried out through standard echocardiographic windows in studies of normal volunteers and patients with documented scar from remote infarct or with hypertrophic cardiomyopathy. Results of this research should permit the implementation of appropriate compensation for the effects of anisotropy and thus broaden the diagnostic power of ultrasound by contributing to the foundation of tissue characterization as a complementary modality to high resolution ultrasonic imaging.